Natural product library screening identifies Darutigenol for the treatment of myocardial infarction and ischemia/reperfusion injury

作者：Kun Liu, Li Zheng, Qian-Yu Huang, Hongji Li, Cheng Li, Hui Zhao, Zipeng Ye, Hao Wang, Xufeng Qi, Meng Wang · 发表于：Chinese Medicine · 年份：2025 · DOI：10.1186/s13020-025-01141-x · 被引用次数：2 · 研究领域：Cardiac Fibrosis and Remodeling、Medicinal Plants and Bioactive Compounds、Cardiac Ischemia and Reperfusion

INTRODUCTION: Ischemic heart diseases are the leading cause of death worldwide due to the inability of regeneration of adult cardiomyocytes (CMs). Natural products from medical herbs are an important source of innovative drugs for many diseases including cardiovascular diseases. OBJECTIVES: In this study, we set out to screen novel small-molecule therapies from natural products to protect heart against ischemic injury. METHODS: High-throughput screening was performed using a natural product library to identify the potential small molecules which can promote survival of CMs under ischemic and ischemic/reperfusion conditions. In addition, myocardial infarction (MI) and ischemia/reperfusion (I/R) mice models were used to evaluate the in vivo effects of the screened candidate. We also applied various analysis including cell viability, qPCR, Western blot, immunofluorescent staining, echocardiography, Masson's staining, TTC staining, and network pharmacology. RESULTS: High-throughput screening showed that the small molecule compound Darutigenol (Dar), derived from the Chinese traditional herb Herba Siegesbeckiae, could significantly promote CM survival and proliferation under ischemic conditions. Moreover, I/R-induced CM apoptosis and ROS generation could be significantly reduced by Dar treatment. In addition, in vivo administration of Dar was able to attenuate MI- and I/R-induced cardiac injury in adult mice by decreasing fibrosis and apoptosis, thereby improving cardiac function....